Analogues of Tri-o-thymotide (TOT) and Tri-o-carvacrotide (TOC) by Direct Bromination of TOT and TOC

Mono-, di-, tri-, tetra-, and pentabrominated tri-o-thymotide (TOT) analogues (3‒7) and mono-, di-, tri-, and tetrabrominated tri-o-carvacrotide (TOC) analogues (9‒12) were synthesized by direct bromination of TOT and TOC. Total yields of about 60% were realized from TOT or TOC. The degree of bromination of the methyl group depended upon the reaction temperature and ratio of TOT (TOC):NBS. Tribromo-TOT (5) was generated in the greatest yield using a 1:18 ratio of TOT:NBS. No bromination occured in the isopropyl group. Structure assignments were made for all new analogues. The conformational mobility of some of these analogues as well as the effect of solvents on the proton chemical shifts were studied by NMR techniques.